umu.sePublikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Allopregnanolone and mood: studies of postmenopausal women during treatment with progesterone
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
2006 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Introduction. Allopregnanolone and pregnanolone (neuroactive metabolites of progesterone) act as positive modulators of the GABAA receptor system which is the major inhibitory system in CNS. Contradictory results on the effect of GABAA receptor modulators are reported. Beneficial properties such as anaesthesia, sedation, and anxiolysis are reported as well as adverse, anxiogenic and aggressive effects. It has been suggested that GABAA receptor agonists have bimodal effects. Low concentrations increase an adverse, anxiogenic effect, whereas higher concentrations show beneficial, calming properties.

Aims. To investigate if progesterone treatment induces adverse mood in postmenopausal women and if the severity in mood symptoms is related to progesterone, allopregnanolone or pregnanolone serum concentrations. To evaluate differences in steroid concentrations induced by different doses and routes of administration of progesterone.

Methods. Two randomised, placebo-controlled, double-blind crossover studies of postmenopausal women were performed. Subjects were treated with estradiol continuously. Different doses of progesterone, given vaginally or orally, were added sequentially during the last 14 days of each treatment cycle. Daily symptom ratings were kept using a validated rating scale. Blood samples for progesterone, allopregnanolone and pregnanolone analyses were collected during each treatment cycle. A study regarding the pharmacokinetics after ingestion of low-dose oral progesterone was conducted with postmenopausal women. Blood samples for the analyses of progesterone, allopregnanolone and pregnanolone were collected and pharmacokinetic parameters were calculated.

Results. Certain postmenopausal women on sequential HT with vaginal and oral progesterone experience mood deterioration during the progesterone phase while on a low dose of progesterone but not on higher doses or the placebo. Negative mood symptoms occurred when the serum concentration of allopregnanolone was similar to endogenous luteal phase levels, whereas lower and higher concentrations had no effect on mood. Pharmacokinetic analyses show that low-dose oral progesterone can be used as a prodrug to allopregnanolone when the aim is to achieve physiological concentrations of allopregnanolone.

Conclusions. A bimodal association between allopregnanolone concentration and adverse mood is observed in postmenopausal women treated with progesterone. The addition of low-dose progesterone to estradiol induces adverse mood in postmenopausal women, whereas higher doses and placebo have no mood-deteriorating effect.

sted, utgiver, år, opplag, sider
Umeå: Klinisk vetenskap , 2006. , s. 142
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1022
Emneord [en]
Obstetrics and gynaecology, Progesterone, Allopregnanolone, GABA, mood, bimodal
Emneord [sv]
Obstetrik och kvinnosjukdomar
Identifikatorer
URN: urn:nbn:se:umu:diva-785ISBN: 91-7264-065-0 (tryckt)OAI: oai:DiVA.org:umu-785DiVA, id: diva2:144527
Disputas
2006-06-01, hörsal Betula, 6M, Norrlands Universitetssjukhus, Umeå, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2006-05-03 Laget: 2006-05-03 Sist oppdatert: 2011-04-07bibliografisk kontrollert
Delarbeid
1. Progesterone effects during sequential hormone replacement therapy
Åpne denne publikasjonen i ny fane eller vindu >>Progesterone effects during sequential hormone replacement therapy
Vise andre…
2003 (engelsk)Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 148, nr 5, s. 571-577Artikkel i tidsskrift (Fagfellevurdert) Published
Identifikatorer
urn:nbn:se:umu:diva-5130 (URN)12720542 (PubMedID)
Tilgjengelig fra: 2006-05-03 Laget: 2006-05-03 Sist oppdatert: 2018-06-09bibliografisk kontrollert
2. Relationship between allopregnanolone and negative mood in postmenopausal women taking sequential hormone replacement therapy with vaginal progesterone.
Åpne denne publikasjonen i ny fane eller vindu >>Relationship between allopregnanolone and negative mood in postmenopausal women taking sequential hormone replacement therapy with vaginal progesterone.
Vise andre…
2005 (engelsk)Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 30, nr 2, s. 212-224Artikkel i tidsskrift (Fagfellevurdert) Published
Emneord
Administration; Intravaginal, Adult, Affect/physiology, Cross-Over Studies, Dose-Response Relationship; Drug, Double-Blind Method, Drug Therapy; Combination, Estradiol/administration & dosage, Female, Hormone Replacement Therapy/*adverse effects/psychology, Humans, Middle Aged, Mood Disorders/blood/*chemically induced, Postmenopause/blood/*drug effects/psychology, Pregnanolone/*administration & dosage/*adverse effects/blood, Progesterone/*administration & dosage/adverse effects/blood, Severity of Illness Index
Identifikatorer
urn:nbn:se:umu:diva-16940 (URN)10.1016/j.psyneuen.2004.07.003 (DOI)15471618 (PubMedID)
Tilgjengelig fra: 2007-10-22 Laget: 2007-10-22 Sist oppdatert: 2018-06-09bibliografisk kontrollert
3. Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone.
Åpne denne publikasjonen i ny fane eller vindu >>Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone.
Vise andre…
2006 (engelsk)Inngår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 54, nr 3, s. 238-244Artikkel i tidsskrift (Fagfellevurdert) Published
Emneord
Administration; Oral, Adult, Aged, Area Under Curve, Estrogen Replacement Therapy, Female, Humans, Middle Aged, Postmenopause, Pregnanolone/administration & dosage/blood/pharmacokinetics, Progesterone/administration & dosage/blood/*pharmacokinetics
Identifikatorer
urn:nbn:se:umu:diva-10381 (URN)10.1016/j.maturitas.2005.11.005 (DOI)16406399 (PubMedID)
Tilgjengelig fra: 2008-09-02 Laget: 2008-09-02 Sist oppdatert: 2018-06-09bibliografisk kontrollert
4. Allopregnanolone concentration and mood: a bimodal association in postmenopausal women treated with oral progesterone.
Åpne denne publikasjonen i ny fane eller vindu >>Allopregnanolone concentration and mood: a bimodal association in postmenopausal women treated with oral progesterone.
Vise andre…
2006 (engelsk)Inngår i: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 187, nr 2, s. 209-221Artikkel i tidsskrift (Fagfellevurdert) Published
Emneord
Administration; Oral, Affect/*drug effects, Climacteric/*drug effects, Cross-Over Studies, Dose-Response Relationship; Drug, Double-Blind Method, Drug Administration Schedule, Drug Therapy; Combination, Estradiol/analogs & derivatives/pharmacology, Female, Hormone Replacement Therapy, Humans, Medroxyprogesterone 17-Acetate/blood/*pharmacology, Middle Aged, Pregnanolone/*blood
Identifikatorer
urn:nbn:se:umu:diva-16547 (URN)10.1007/s00213-006-0417-0 (DOI)16724185 (PubMedID)
Tilgjengelig fra: 2007-10-05 Laget: 2007-10-05 Sist oppdatert: 2018-06-09bibliografisk kontrollert

Open Access i DiVA

fulltekst(2906 kB)1050 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 2906 kBChecksum MD5
8cef86cc503826822da9006834c45f7b9374ea28c046231a6634aea90680fba643b97849
Type fulltextMimetype application/pdf

Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 1050 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

isbn
urn-nbn

Altmetric

isbn
urn-nbn
Totalt: 1424 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf